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W. Ma, S.-Z. Wang; Sox2 Regulates bFGF and PEDF Expression in Normal and Damaged Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5403.
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Sox2 is of the 4 genes required to turn human skin cells back to pluripotent stem cells. This study investigates whether and how chick Sox2 regulates retinal development, function, and responses to damages, focusing on its induction or suppression of the expression of bFGF and PEDF.
The effect of Sox2 on the expression of bFGF and PEDF was studied using gain-of-function experiments. Retrovirus (RCAS-Sox2) was used to drive Sox2 expression in the developing retina, cultured retinal glial cells, and cultured RPE cells. Expression of bFGF and PEDF, as well as Sox2, was examined with in situ hybridization and semi-quantitative RT-PCR. Damages to chick retinas were achieved with NMDA.
In the developing retina, bFGF expression was mainly detected in what believed to be Muller glial cells. The same is true for Sox2 expression, except that significant expression of Sox2 was also observed in a subset of amacrine cells. In NMD-damaged retina, both sox2 and bFGF expression was increased. In retinas infected RCAS-Sox2, the level of bFGF expression was increased compared with those infected with RCAS-GFP. Increased bFGF expression was also observed with glial cell cultures infected with RCAS-Sox2. On the other hand, PEDF expression was reduced in the retina and in glia cell culture infected with RCAS-Sox2. In cultured RPE cells, PEDF expression was reduced by either Sox2 or bFGF, and deeper reduction was observed with both together than either alone.
These results suggest that Sox2 may promote bFGF expression and suppress PEDF expression in normal and NMDA-damaged retina. This specific function of Sox2 may be partially responsible for its important role in maintaining stem cell properties.
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